microRNAs signatures as potential biomarkers of structural cardiotoxicity in human-induced pluripotent stem-cell derived cardiomyocytes.
Biomarkers
Cardiotoxicity
hiPSC-CM
miRNA
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
16
12
2021
accepted:
14
03
2022
pubmed:
30
4
2022
medline:
3
6
2022
entrez:
29
4
2022
Statut:
ppublish
Résumé
Identification of early biomarkers of heart injury and drug-induced cardiotoxicity is important to eliminate harmful drug candidates early in preclinical development and to prevent severe drug effects. The main objective of this study was to investigate the expression of microRNAs (miRNAs) in human-induced pluripotent stem cell cardiomyocytes (hiPSC-CM) in response to a broad range of cardiotoxic drugs. Next generation sequencing was applied to hiPSC-CM treated for 72 h with 40 drugs falling into the categories of functional (i.e., ion channel blockers), structural (changes in cardiomyocytes structure), and general (causing both functional and structural) cardiotoxicants as well as non-cardiotoxic drugs. The largest changes in miRNAs expression were observed after treatments with structural or general cardiotoxicants. The number of deregulated miRNAs was the highest for idarubicin, mitoxantrone, and bortezomib treatments. RT-qPCR validation confirmed upregulation of several miRNAs across multiple treatments at therapeutically relevant concentrations: hsa-miR-187-3p, hsa-miR-146b-5p, hsa-miR-182-5p (anthracyclines); hsa-miR-365a-5p, hsa-miR-185-3p, hsa-miR-184, hsa-miR-182-5p (kinase inhibitors); hsa-miR-182-5p, hsa-miR-126-3p and hsa-miR-96-5p (common some anthracyclines, kinase inhibitors and bortezomib). Further investigations showed that an upregulation of hsa-miR-187-3p and hsa-miR-182-5p could serve as a potential biomarker of structural cardiotoxicity and/or an additional endpoint to characterize cardiac injury in vitro.
Identifiants
pubmed: 35488128
doi: 10.1007/s00204-022-03280-8
pii: 10.1007/s00204-022-03280-8
doi:
Substances chimiques
Anthracyclines
0
Biomarkers
0
MicroRNAs
0
Bortezomib
69G8BD63PP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2033-2047Subventions
Organisme : Walloon region
ID : DGO6 (Convention N°7245)
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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